Elevated red blood cell distribution width-to-albumin ratio and incident cancer risk: A prospective cohort study.

10575 Background: Cancer remains a leading cause of global morbidity and mortality, underscoring the need for accessible biomarkers for early detection and risk stratification. The red blood cell distribution width-to-albumin ratio (RAR) is an emerging composite index integrating markers of erythropoietic stress and nutritional status/hepatic dysfunction, often dysregulated in malignancy and systemic inflammation. Elevated RAR correlates with worse outcomes in patients with sepsis and various cancers; however, its association with incident cancer risk in large prospective cohorts remains uncharacterized. Methods: Using UK Biobank data, we conducted a prospective cohort study with 5:1 propensity score matching, yielding an analytic cohort of 112,107 participants (18,916 with elevated RAR, 93,191 with normal RAR). Elevated RAR was defined as > 95th percentile (> 3.48 %·dL/g) among cancer-free participants at baseline. Matching balanced groups by age, sex, ethnicity, socioeconomic status, BMI, smoking, alcohol use, diabetes, chronic kidney disease, and family history of cancer. Adjusted Cox proportional hazards regression was utilized to assess associations between elevated RAR and incident cancer. We also performed a 2-year landmark analysis to evaluate reverse causation. Hazard ratios (HRs) with 95% confidence intervals (CIs) are reported. Results: During median follow-up of 15.4 years (1.55 million person-years), 21,307 incident cancers occurred. Elevated RAR was significantly associated with 23% increased overall cancer risk (HR 1.23; 95% CI 1.18-1.27). Cancer-specific analyses revealed strongest associations for hematologic malignancies (HR 1.91; 95% CI 1.70-2.14), including acute myeloid leukemia (HR 2.22; 95% CI 1.37-3.60) and chronic myeloid leukemia (HR 2.78; 95% CI 1.23-6.31). Significant associations were also observed for gastric (HR 2.12; 95% CI 1.57-2.86), liver (HR 1.90; 95% CI 1.38-2.62), lung (HR 1.45; 95% CI 1.27-1.66), and colon cancer (HR 1.48; 95% CI 1.28-1.72). No significant association was observed for breast (HR 1.06; 95% CI 0.96-1.17) or prostate cancer (HR 0.94; 95% CI 0.84-1.05). A 2-year landmark analysis showed that the association with overall cancer risk remained robust (HR 1.19; 95% CI 1.15-1.24). Conclusions: Elevated RAR is independently associated with increased incident cancer risk, particularly for hematologic, gastrointestinal, and lung cancers. These associations persisted in 2 year landmark analyses, supporting a potential prospective relationship and motivates further evaluation of RAR, a readily calculable index from routinely obtained laboratory values, in cancer risk models.